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1.
Int J Nanomedicine ; 14: 4781-4800, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308658

RESUMO

Advancements in nanotechnology and molecular biology have promoted the development of a diverse range of models to intervene in various disorders (from diagnosis to treatment and even theranostics). Manganese dioxide nanosheets (MnO2 NSs), a typical two-dimensional (2D) transition metal oxide of nanomaterial that possesses unique structure and distinct properties have been employed in multiple disciplines in recent decades, especially in the field of biomedicine, including biocatalysis, fluorescence sensing, magnetic resonance imaging and cargo-loading functionality. A brief overview of the different synthetic methodologies for MnO2 NSs and their state-of-the-art biomedical applications is presented below, as well as the challenges and future perspectives of MnO2 NSs.


Assuntos
Tecnologia Biomédica/métodos , Compostos de Manganês/química , Nanoestruturas/química , Nanotecnologia/métodos , Óxidos/química , Técnicas Biossensoriais , Nanoestruturas/toxicidade , Óxidos/toxicidade , Tamanho da Partícula
2.
Ecotoxicol Environ Saf ; 181: 345-352, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31202935

RESUMO

Nanomaterials are being used increasingly in various areas such as electronic devices manufacture, medicine, mechanical devices production, and even food industry. Therefore, the evaluation of their toxicity is mandatory. Graphene oxide (GO) has been shown to have both positive as well as negative impact on different crop plants, depending on species, dose, and duration of exposure. The current study evaluated the impact of GO sheets at different concentrations (500, 1000 and 2000 mg/L) on physiological, biochemical and genetic levels to determine the possible toxic action. Wheat caryopses were treated with GO for 48 h and 7 days. The germination rate and roots elongation decreased in a dose-response manner, except the sample treated with GO at a concentration of 1000 mg/L. Mitotic index has ascendant trend; its increase may be due to the accumulation of prophases GO induced significant accumulation of the cells with aberrations, their presence suggests a clastogenic/aneugenic effect of these carbon nanomaterials. Regarding enzymatic and non-enzymatic antioxidant system defence, the activity varied depending on the dose of GO. Thus, chlorophyll a pigments content decreased significantly at high dose (2000 mg/L), while the carotenoid pigments had lower content at 500 mg/L of GO, and no statistical difference encountered in case of chlorophyll b amount. The antioxidant enzyme activity (CAT, POD, and SOD) was higher at low dose of GO, indicating the presence of oxidative stress generated as a response to the GO treatment. Also, the free radical scavenging activity of the polyphenolic compounds was enhanced upon GO exposure. The GO accumulation has been identified by transmission electron microscopy only at plumules level, near the intercellular space.


Assuntos
Grafite/toxicidade , Nanoestruturas/toxicidade , Triticum/efeitos dos fármacos , Antioxidantes/metabolismo , Clorofila/metabolismo , Clorofila A/metabolismo , Germinação/efeitos dos fármacos , Estresse Oxidativo , Óxidos/toxicidade , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Plântula/efeitos dos fármacos , Plântula/enzimologia , Plântula/metabolismo , Triticum/enzimologia , Triticum/crescimento & desenvolvimento , Triticum/metabolismo
3.
Chemosphere ; 233: 625-632, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31195266

RESUMO

The response of anaerobic ammonium oxidation (anammox) process and granular sludge in the upflow anaerobic sludge blanket reactor was analyzed under long-term exposure to MnO2 nanoparticles (NPs) (1-200 mg L-1). The addition of 200 mg L-1 MnO2 NPs had a significantly positive effect on nitrogen removal and this system exhibited excellent performance, with a total nitrogen removal efficiency of 93.1%. Moreover, the specific anammox activity enhanced with increasing concentrations of MnO2 NPs up to the maximum value of 657.3 ±â€¯9.3 mg TN g-1 VSS d-1 under MnO2 NPs concentration of 200 mg L-1. This value was approximately 1.6-fold higher than that of the reactor in the absence of MnO2 NPs. The extracellular polymeric substances and settling velocity were both increased with MnO2 NPs addition. Meanwhile, the high-throughput sequencing results revealed that MnO2 NPs increased the relative abundance of dominant bacteria (Candidatus Kuenenia) from 17.3% at the absence of MnO2 NPs to 23.9% at 200 mg L-1 MnO2 NPs, which resulted in a higher efficiency of biological nitrogen removal on the anammox system. These results indicated that MnO2 NPs enhanced nitrogen removal performance of anammox process.


Assuntos
Reatores Biológicos/microbiologia , Microbiota , Nanopartículas/toxicidade , Óxidos/toxicidade , Anaerobiose , Bactérias , Compostos de Manganês , Nitrogênio , Oxirredução , Esgotos/microbiologia
4.
Talanta ; 201: 388-396, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31122439

RESUMO

Ascorbic acid (AA) is an essential vitamin and plays an irreplaceable role in humans' daily life. Therefore, it is of profound significance to develop effective strategies for AA sensing. Herein, a novel bi-functional sensing strategy was developed by using carbon dots (CDs) and MnO2 nanosheet as the fluorometric/magnetic signal source. When AA was absence, the fluorescence of CDs was quenched by MnO2 nanosheet due to the inner filter effect. Neither the fluorescence nor magnetic signal of the nanoprobe can be detected. In the presence of AA, a redox reaction occurred between MnO2 nanosheet and AA resulting in the generation of magnetic resonance imaging (MRI) response Mn2+ and decomposing of MnO2 nanosheet structure, thus leading to the recovery of CDs fluorescence. The detection limit of the AA was determined to be 2.89 µM with a linear range of 0-80 µM in fluorescence mode, and detection limit of 0.776 µM with a linear range of 0-80 µM in MRI mode when used transverse relaxation rate as signal. Furthermore, the developed fluorometric/magnetic bi-functional nanoprobe showed good biocompatibility, high response rate, high selectivity towards AA and could be used to analyses AA in real samples. Moreover, in vivo imaging of AA in mice was achieved in magnetic mode. The fluorometric/magnetic bi-function sensor for AA detection was introduced, which provided a novel strategy for sensor design based on CDs.


Assuntos
Ácido Ascórbico/análise , Corantes Fluorescentes/química , Imagem por Ressonância Magnética/métodos , Compostos de Manganês/química , Óxidos/química , Pontos Quânticos/química , Espectrometria de Fluorescência/métodos , Animais , Ácido Ascórbico/química , Ácido Ascórbico/metabolismo , Fluorescência , Corantes Fluorescentes/toxicidade , Limite de Detecção , Fenômenos Magnéticos , Masculino , Camundongos Endogâmicos BALB C , Oxirredução , Óxidos/toxicidade , Pontos Quânticos/toxicidade
5.
Sci Total Environ ; 681: 350-364, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31117016

RESUMO

This work deals with the fabrication of metallosurfactants derived cobalt oxide and hydroxide nanosuspensions (Ns) by microemulsion method and their antimicrobial, cytotoxic, genotoxic, antioxidant and cytostatic activity have been investigated. The methodology used is environmentally compliant as no external reducing agent was used. Three metallosurfactants i.e. CoCTAC (Bishexadecyltrimethylammonium cobalt tetrachloride), CoDDA (Bisdodecylamine cobalt dichloride) and CoHEXA (bishexadecylamine cobalt dichloride) were used. Co-metallosurfactants were synthesized, characterized and were utilized for the preparation of mixed microemulsion to yield nanosuspensions. Nanoparticles prepared were characterized using Transmission electron microscopy (TEM), Field Emission Scanning Electron Microscope (FESEM), Energy Dispersive X-ray Spectroscopy (EDS), X-ray Diffraction (XRD), UV-vis spectroscopy and Zeta potential. The nanoparticles were found to be spherical, with size range 1-5 nm, for all the three precursors. Further, their cytotoxicity, genotoxicity, and antimicrobial activity were investigated against Staphylococcus aureus (S. aureus). To evaluate these activities, techniques such as gram staining method, agar well diffusion, and colony forming unit count (CFU) were utilized. From all these experiments it was confirmed that CoCTAC Ns has maximum antimicrobial activity against multiple medicine resistant S. aureus. Circular dichroism and gel electrophoresis also validated the vigorous genotoxic effect of CoCTAC Ns. The antimicrobial activity trend investigated from CFU experiment was CoCTAC Ns (2 × 105 CFU/mL) > CoDDA Ns (17 × 105 CFU/mL) > CoHEXA Ns (46.5 × 105 CFU/mL). FESEM authenticated the effect of Co Ns on the morphology of S. aureus. Cell shrinkage, formation of holes, change of morphology, and cell wall rupturing was observed for all three cases but most significant antibacterial activity was noted for the case of CoCTAC Ns. In addition, antiproliferative activity was also examined against HepG2 cells (human liver cancer cell line) and HEK293 cells (human embryonic kidney cell line). After 70% confluency of cells, cobalt oxide/hydroxide Ns were added by diluting the nanosuspension in 0.2, 0.4, 0.5, and 0.8% V/V ratio to check the cell viability.


Assuntos
Antibacterianos/toxicidade , Nanopartículas Metálicas/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Tensoativos/toxicidade , Cobalto/toxicidade , Óxidos/toxicidade
6.
Sci Total Environ ; 677: 1-8, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31051379

RESUMO

The ecotoxicological evaluation of combined sewer overflow (CSO) disinfectants, with their degradation products, is important for ensuring safe use. For this form of toxicity, data for organisms representing different trophic levels are needed. We studied the toxicity of the alternative disinfectants peracetic acid (PAA), performic acid (PFA) and chlorine dioxide (ClO2) and their degradation products hydrogen peroxide (H2O2) and chlorite (ClO2-) on Vibrio fischeri and Daphnia magna. ClO2 was more toxic to D. magna (EC50 < 0.09 mg/L) and PFA was most toxic to V. fischeri (EC50 0.24 mg/L). EC50 of PFA, PAA, ClO2, H2O2 and ClO2- on D. magna were 0.85, 0.78, <0.09, 3.46 and 0.36 mg/L, respectively. Similarly, EC50 of PFA, PAA, ClO2, H2O2 and ClO2- on V. fischeri were 0.24, 0.42, 1.10, 5.67 and 30.93 mg/L, respectively. For both PFA and ClO2, the degradation in water was faster than for PAA, H2O2 and chlorite. Using these data together with literature values, we derived environmental quality standards. By combining these with typical concentrations of disinfectants used for CSOs, we estimated the dilution required for discharging CSOs after disinfection, which can be used for quick assessment of the environmental feasibility of disinfection systems at specific CSO sites. Minimal dilutions in the receiving water, in the orders of 44, 70 or 138-fold, are needed for ClO2, PFA and PAA, respectively. This highlights PFA as the most widely applicable disinfectant, taking into account both its efficiency and the lower risk of unwanted environmental effects.


Assuntos
Aliivibrio fischeri/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Desinfetantes/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Cloretos/toxicidade , Compostos Clorados/toxicidade , Desinfecção , Formiatos/toxicidade , Peróxido de Hidrogênio/toxicidade , Óxidos/toxicidade , Ácido Peracético/toxicidade , Esgotos
7.
Sci Total Environ ; 673: 810-820, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31005017

RESUMO

Graphene oxide (GO) has wide engineering applications in various areas, including electronics, energy storage, pharmaceuticals, nanomedicine, environmental remediation and biotechnology, because of its unique physico-chemical properties. In the present study, the risk-related information of GO was evaluated to examine the potential ecological and health risks of developmental toxicity. Although the overall developmental toxicity of GO has been well characterized in zebrafish, however, its release effect at a certain concentration of living organisms with specific cardiovascular defects remains largely elusive. Therefore, this study was conducted to further evaluate the toxicity of GO on embryonic development and cardiovascular defects in zebrafish embryos used as an in-vivo animal model. As a result, the presence of GO at a small concentration (0.1-0.3 mg/mL) does not affect the embryonic development. However, GO at higher concentrations (0.4-1 mg/mL) induces significant embryonic mortality, increase heartbeat, delayed hatching, cardiotoxicity, cardiovascular defects, retardation of cardiac looping, increased apoptosis and decreased hemoglobinization. These results provide valuable information that can be used to study the eco-toxicological effects of GO for assessing its bio-safety according to environmental concentration. In addition, the present results would also be usefully utilized for understanding the environmental risks associated with GO on human health in general.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Grafite/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Recuperação e Remediação Ambiental , Óxidos/toxicidade
9.
Ann Pharm Fr ; 77(2): 126-135, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30709547

RESUMO

OBJECTIVES: This work aims at getting more insights into the distinct behavior of S-oxide derivatives of thiocarbonyl-containing antitubercular drugs, in order to better understand their mechanism of action and toxicity. METHODS: Computational calculation of relative free energy (ΔΔG) of S-oxide tautomers (sulfine R-C [SO]NH2), sulfenic acid (R-C [S-OH]NH) and sulfoxide (R-C [SHO]NH) derived from thioamide and thiourea antitubercular drugs and an update of the literature data with a new point of view about how the structural features of oxidized primary metabolites (S-oxide) can influence the outcome of the reactions and be determinant for the mechanisms of action and of toxicity of these drugs. RESULTS: The calculated free energy of S-oxide tautomers, derived from thioamide and thiourea-type antitubercular drugs, supported by some experimental results, revealed that S-oxide derivatives could be found under sulfine and sulfenic acid forms depending on their chemical structures. Thiocarbonyl compounds belonging to the thioamide series are firstly oxidized, in the presence of H2O2, into the corresponding S-oxide derivatives that are more stable under the sulfine tautomeric form. Otherwise, S-oxides of thiourea-type (acyclic and cyclic) compounds tend to adopt the sulfenic acid tautomeric form preferentially. While the intermediate ethionamide-SO under sulfine form can be isolated and in the presence of H2O2 can undergo further oxidation by a mechanism yielding radical species that are toxic for Mycobacterium tuberculosis and human, thioacetazone-SO, found mainly into sulfenic acid form, is unstable and sufficiently reactive in biological conditions to intercept different biochemical pathways and manifests thus its toxicity. CONCLUSION: Based on experimental and theoretical data, we propose that S-oxide derivatives of thioamide and thiourea-type antitubercular drugs have preference for distinct tautomeric forms. S-oxide of ethioamide is preferentially under sulfine form whereas S-oxide of thiourea compound as thioacetazone is mainly found under sulfenic acid form. These structural features lead to individual chemical reactivities that might explain the distinct mechanism of action and toxicity observed for the thioamide and thiourea antitubercular drugs.


Assuntos
Antituberculosos/química , Antituberculosos/farmacologia , Óxidos/química , Óxidos/farmacologia , Antituberculosos/toxicidade , Cromatografia Líquida de Alta Pressão , Óxidos/toxicidade , Estereoisomerismo , Ácidos Sulfênicos/química , Tioamidas/química , Tioamidas/farmacologia , Tioamidas/toxicidade , Tioureia/química , Tioureia/farmacologia , Tioureia/toxicidade
10.
Sci Total Environ ; 653: 675-683, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30759593

RESUMO

The increasing occurrence of engineered nanoparticles (NPs) in soils may decrease water uptake in crops, followed by lower crop yield and quality. As one of the most common rare earth oxide NPs, lanthanum oxide (La2O3) NPs may inhibit the relative expressions of aquaporin genes, thus reduce water uptake. In the present study, maize plants were exposed to different La2O3 NPs concentrations (0, 5, 50 mg L-1) for 72 h and 144 h right after the first leaf extended completely. Our results revealed that water uptake was reduced by La2O3 NPs through accelerating the development of apoplastic barriers in maize roots. The level of abscisic acid, determined by using ultra high performance liquid chromatography-tandem mass spectrometry, was increased upon La2O3 NPs exposure. Furthermore, ZmPAL, ZmCCR2 and ZmCAD6, the core genes specific for biosynthesis of lignin, were up-regulated by 3-13 fold in roots exposed to 50 mg L-1 La2O3 NPs. However, ZmF5H was suppressed, indicating that lignin with S units could be excluded for the formed lignin in apoplastic barriers upon La2O3 NPs exposure. The level of essential component of apoplastic barriers - lignin was increased by 1.5-fold. The early development of apoplastic barriers was observed, and stomatal conductance and transpiration rate of La2O3 NPs-treated plants were significantly decreased by 63%-83% and 42%-86%, respectively, as compared to the control. The lignin enriched apoplastic barriers in juvenile maize thus led to the reduction of water uptake, subsequently causing significant growth inhibition. This is the first study to show early development of root apoplastic barriers upon La2O3 NPs exposure. This study will help us better understand the function of apoplastic barriers in roots in response to NPs, further providing fundamental knowledge to develop safer and more efficient agricultural nanotechnology.


Assuntos
Lantânio/toxicidade , Lignina/metabolismo , Nanopartículas/toxicidade , Óxidos/toxicidade , Poluentes do Solo/toxicidade , Água/metabolismo , Zea mays/efeitos dos fármacos , Transporte Biológico , Relação Dose-Resposta a Droga , Lantânio/química , Nanopartículas/química , Óxidos/química , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Poluentes do Solo/química , Zea mays/metabolismo
11.
Ecotoxicol Environ Saf ; 163: 456-464, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30075448

RESUMO

In Caenorhabditis elegans, mutation of mlt-7 causes the deficits in epidermal barrier. Using the nematodes with epidermal-specific RNA interference (RNAi) knockdown of mlt-7 as a genetic tool, we found that epidermal-specific RNAi knockdown of mlt-7 resulted in a susceptibility to graphene oxide (GO) toxicity, and enhanced GO accumulation in the body. Epidermal-development related proteins of BLI-1 and IFB-1 acted as downstream targets of MLT-7, and mediated the function of MLT-7 in maintaining the epidermal barrier. Antimicrobial proteins of NLP-30 and CNC-2 also acted as downstream targets of MLT-7 in the regulation of GO toxicity. Epidermal-specific RNAi knockdown of nlp-30 or cnc-2 enhanced GO toxicity and accumulation in bli-1(RNAi) or ifb-1(RNAi) nematodes. Our data highlights the importance of maintaining normal epidermal barrier for nematodes against the GO toxicity.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/efeitos dos fármacos , Grafite/toxicidade , Óxidos/toxicidade , Pele/metabolismo , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Grafite/farmacocinética , Mutação , Óxidos/farmacocinética , Interferência de RNA
12.
Ecotoxicol Environ Saf ; 164: 530-539, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30149351

RESUMO

The wide application of engineered nanoparticles to remove heavy metals in aquatic environments has raised concerns over nanomaterial-adsorbed heavy metal toxicity. To ensure safe use of nanomaterial-heavy metal composites, understanding their biological effects at the molecular level is crucial. In the present study, we used the Illumina HiSeq technology to study the transcriptome changes induced by Cd2+ and nano-manganese dioxide- or nano-hydroxyapatite-adsorbed CdCl2 composites (nMnO2-Cd, nHAP20-Cd, and nHAP40-Cd) in zebrafish liver cells. We identified 545 differentially expressed genes (DEGs), 33 of which were in common between the nMnO2-Cd, nHAP20-Cd, and nHAP40-Cd groups. The DEGs could be classified in four categories: hydrolases (enzymes involved in various physiological functions, including digestion, immune response, blood coagulation, and reproduction), biological binding (FMN-, actin- and metal ion-binding), metabolic enzymes (e.g., ceramidase, alpha-amylase, carboxylic ester hydrolase, and carboxypeptidase), and cell structure (cell surface, intermediate filament, and muscle myopen protein). The DEGs identified in this study are potentially useful markers to understand the physiological responses induced by Cd2+ and nano-Cd composites in zebrafish liver.


Assuntos
Cádmio/toxicidade , Fígado/efeitos dos fármacos , Nanoestruturas , Peixe-Zebra/metabolismo , Adsorção , Animais , Cádmio/metabolismo , Cloreto de Cádmio/metabolismo , Cloreto de Cádmio/toxicidade , Durapatita/toxicidade , Perfilação da Expressão Gênica , Fígado/metabolismo , Compostos de Manganês , Óxidos/toxicidade , Transcriptoma , Peixe-Zebra/genética
13.
Ecotoxicol Environ Saf ; 162: 192-200, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-29990731

RESUMO

Nanographene oxide (nGO) has been recently proposed as a new antitumoral therapeutic agent, drug delivery carrier and gene transfection vehicle, among others. Treatment is carried out by hyperthermia induced by infrared irradiation. After treatment, the nanosystems will be inevitably excreted and released to the environment. To understand the potential impacts of pegylated nGO (nGO-PEG), three key species from different trophic levels were used: the green micro-algae Raphidocelis subcapitata (growth inhibition test), the cladocera Daphnia magna (acute and chronic tests), and the fish Danio rerio (fish embryo test). Besides a regular standard procedure to assess toxicity, and considering the mode of action of nGO-PEG in cancer treatment, a simultaneous infrared lamp exposure was carried out for D. magna and D. rerio. Additionally, and taking advantage of the phenotypic transparency of D. magna, nGO-PEG was fluorescently tagged to evaluate the potential uptake of nGO-PEG. The R. subcapitata growth inhibition test showed effects during the first 48 h, recovering till the end of the test (96 h). No acute or chronic effects were observed for D. magna, under standard or infrared light exposures although confocal microscope images showed nGO-PEG uptake. Very small percentages of mortality and abnormalities were observed in D. rerio exposed with and without the infrared lamp. Although low hazard may be expected for nGO-PEG in aquatic ecosystems, further studies with species with different life traits should be accomplished, in order to derive more accurate conclusions.


Assuntos
Grafite/toxicidade , Óxidos/toxicidade , Polietilenoglicóis/toxicidade , Animais , Antineoplásicos , Clorófitas/efeitos dos fármacos , Clorófitas/crescimento & desenvolvimento , Daphnia/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Embrião não Mamífero/efeitos dos fármacos , Cadeia Alimentar , Grafite/química , Óxidos/química , Polietilenoglicóis/química , Testes de Toxicidade/métodos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia
14.
Acta Biochim Biophys Sin (Shanghai) ; 50(8): 733-739, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29889218

RESUMO

NAD(P)H:quinone oxidoreductase 1 (NQO1), a phase II flavoenzyme that catalyzes reduction reactions to protect cells against electrophiles and oxidants, is involved in tumorigenesis. Altered methylation of the NQO1 gene has been observed and is speculated to result in aberrant NQO1 expression in rat cells undergoing chemical carcinogenesis, although this has not been proven experimentally. In this study, we first investigated the potential epigenetic mechanisms underlying the phenomenon of NQO1 differential expression in individual subclones of rat arsenic-transformed lung epithelial cells (TLECs). NQO1 expression of TLEC subclones with or without 5-aza-2'-deoxycytidine (5-Aza-CdR) treatment was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot analysis, and real-time PCR. Methylation status of the NQO1 promoter in TLEC subclones was analyzed by bisulfite sequencing. Transcriptional activity of NQO1 promoter in vitro methylated was determined by luciferase assay using a CpG-free luciferase reporter driven by the NQO1 promoter region (-435 to +229). We found that non-CpG island (non-CpGI) within the NQO1 promoter was hyper- or hypo-methylated in TLEC subclones and corresponded to low and high gene expressions, respectively. Following the treatment with 5-Aza-CdR, transcription of the NQO1 gene in the hypermethylated subclones was restored, accompanied by demethylation of the NQO1 promoter. In vitro promoter methylation almost completely silenced reporter activity in TLECs. These results indicate that DNA methylation of the non-CpGI promoter contributes to epigenetic silencing of NQO1 in rat TLECs.


Assuntos
Metilação de DNA , Células Epiteliais/metabolismo , NAD(P)H Desidrogenase (Quinona)/genética , Regiões Promotoras Genéticas/genética , Animais , Trióxido de Arsênio , Arsenicais , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Linhagem Celular Transformada , Transformação Celular Neoplásica/efeitos dos fármacos , Ilhas de CpG/genética , Decitabina , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Óxidos/toxicidade , Ratos
15.
Bratisl Lek Listy ; 119(6): 379-384, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29947239

RESUMO

AIM: Manganese dioxide magnetic nanoparticle (MnO2-NP) with specific size range from 30 to 60 nm has widespread application in magnetic resonance imaging, medicine and drug delivery in exposed humans and animals. Manganese nanoparticles could affect hippocampus tissue and impose abnormal cognitive functions such as manganese ion. Therefore, to investigate whether MnO2-NP is damaging hippocampus tissue and inducing molecular and neurobehavioral abnormalities, we administrated different doses of synthesized nanoparticle to rats and measured behavioral, biochemical and histological parameters by standard methods. RESULTS: Results showed that the treatment of rats with MnO2-NP during 15 days induced oxidative stress and reduced catecholamine content in hippocampus tissue. MnO2-NP affected hippocampus tissue appearance by increasing the number of apoptotic and necrotic cells suggested that approved nanoparticle penetrated blood brain barrier and reached the hippocampal cells. Interestingly, all biochemical and histological effects of MnO2-NP were dose dependent. CONCLUSIONS: By considering that hippocampus plays an important role in cognitive function, behavioral abnormalities in intoxicated rats were predictable and nanoparticle administrated rats showed depression like behavioral signs dose dependently. Based on our results and previous studies that confirmed neurotoxicity of MnO2-NP in µg dose rang, the application of this nanoparticles should be limited and their waste should be neutralized before their release to the environment (Fig. 4, Ref. 31).


Assuntos
Comportamento Animal/efeitos dos fármacos , Transtornos Cognitivos/induzido quimicamente , Nanopartículas/toxicidade , Doenças do Sistema Nervoso/induzido quimicamente , Óxidos/toxicidade , Transtornos Parkinsonianos/induzido quimicamente , Animais , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Humanos , Masculino , Compostos de Manganês , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
16.
J Agric Food Chem ; 66(20): 5221-5228, 2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-29709169

RESUMO

1,2-Dehydropyrrolizidine alkaloids (PA) and PA- N-oxides (PANO) are phytotoxins, which presumably occur in more than 6,000 plant species worldwide. Plants containing PA/PANO are responsible for various food and feed poisonings recorded for decades. Main reasons of exposition of consumers and livestock are contaminations of food and animal feed with parts, seeds, pollen, or nectar of PA-containing plants. Concerning stability, effects of processing on PA were mainly investigated in the past. The current study examined the behavior of PA/PANO in unprocessed matrices peppermint tea, hay, and honey during storage. Blank samples were fortified with PA/PANO or contaminated with blueweed ( Echium vulgare) and ragwort ( Senecio jacobaea) and stored for 182 d. The time-series analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmed that all 25 analyzed PA/PANO compounds remained stable in herbal samples. However, the results showed a very fast decrease of PANO in honey samples within hours. These results were discussed with respect to potential consequences for health risk assessment.


Assuntos
Ração Animal/análise , Bebidas/análise , Echium/química , Mel/análise , Mentha piperita/química , Alcaloides de Pirrolizidina/química , Senécio/química , Contaminação de Alimentos/análise , Armazenamento de Alimentos , Óxidos/química , Óxidos/toxicidade , Alcaloides de Pirrolizidina/toxicidade , Espectrometria de Massas em Tandem
17.
Sci Total Environ ; 635: 947-955, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29710616

RESUMO

Despite the fact that the demand for graphene and its derivatives in commercial applications is still growing, many aspects of its toxicity and biocompatibility are still poorly understood. Graphene oxide, which is released into the environment (air, soil and water) as so-called nanowaste or nanopollution, is able to penetrate living organisms. It is highly probable that, due to its specific nature, it can migrate along food chains thereby causing negative consequences. Our previous studies reported that short-term exposure to graphene oxide may increase the antioxidative defense parameters, level of DNA damage, which results in numerous degenerative changes in the gut and gonads. The presented research focuses on reproductive dysfunction and cellular changes in Acheta domesticus after exposure to GO nanoparticles in food (concentrations of 20 and 200 µg·g-1 of food) throughout their entire life cycle. The results showed that long-term exposure to GO caused a significant decrease in the reproductive capabilities of the animals. Moreover, the next generation of A. domesticus had a lower cell vitality compared to their parental generation. It is possible that graphene oxide can cause multigenerational harmful effects.


Assuntos
Grafite/toxicidade , Gryllidae/efeitos dos fármacos , Nanopartículas/toxicidade , Óxidos/toxicidade , Animais , Exposição Dietética , Fertilidade/efeitos dos fármacos , Testes de Toxicidade Crônica
18.
Ecotoxicol Environ Saf ; 159: 221-231, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29753824

RESUMO

The effects of graphene oxide (GO) carbon nanomaterials on ecosystems have been well characterized, but the toxicity of GO at predicted environmental concentrations to living organisms at the protein level remain largely unknown. In the present work, the adverse effects and mechanisms of GO at predicted environmental concentrations were evaluated by integrating proteomics and standard analyses for the first time. The abundances of 243 proteins, including proteins involved in endocytosis (e.g., cltcb, arf6, capzb and dnm1a), oxidative stress (e.g., gpx4b, sod2, and prdx1), cytoskeleton assembly (e.g., krt8, krt94, lmna and vim), mitochondrial function (e.g., ndufa10, ndufa8, cox5aa, and cox6b1), Ca2+ handling (e.g., atp1b2a, atp1b1a, atp6v0a1b and ncx4a) and cardiac function (e.g., tpm4a, tpm2, tnni2a.1 and tnnt3b), were found to be notably altered in response to exposure 100 µg/L GO. The results revealed that GO caused malformation and mortality, likely through the downregulation of proteins related to actin filaments and formation of the cytoskeleton, and induced oxidative stress and mitochondrial disorders by altering the levels of antioxidant enzymes and proteins associated with the mitochondrial membrane respiratory chain. Exposure to GO also increased the heart rate of zebrafish larvae and induced pericardial edema, likely by changing the expression of proteins related to Ca2+ balance and cardiac function. This study provides new proteomic-level insights into GO toxicity against aquatic organisms, which will greatly benefit our understanding of the bio-safety of GO and its toxicity at predicted environmental concentrations.


Assuntos
Grafite/toxicidade , Nanoestruturas/toxicidade , Óxidos/toxicidade , Peixe-Zebra , Animais , Frequência Cardíaca/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/metabolismo , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteômica , Peixe-Zebra/anormalidades , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
19.
J Nanobiotechnology ; 16(1): 45, 2018 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-29703212

RESUMO

BACKGROUND: So far, how the animals evade the environmental nanomaterials is still largely unclear. In this study, we employed in vivo assay system of Caenorhabditis elegans to investigate the aversive behavior of nematodes to graphene oxide (GO) and the underlying neuronal basis. RESULTS: In this assay model, we detected the significant aversive behavior of nematodes to GO at concentrations more than 50 mg/L. Loss-of-function mutation of nlg-1 encoding a neuroligin with the function in connecting pre- and post-synaptic neurons suppressed the aversive behavior of nematodes to GO. Moreover, based on the neuron-specific activity assay, we found that the NLG-1 activity in AIY or AIB interneurons was required for the regulation of aversive behavior to GO. The neuron-specific activities of NLG-1 in AIY or AIB interneurons were also required for the regulation of GO toxicity. CONCLUSIONS: Using nlg-1 mutant as a genetic tool, we identified the AIY and AIB interneurons required for the regulation of aversive behavior to GO. Our results provide an important neuronal basis for the aversive response of animals to environmental nanomaterials.


Assuntos
Caenorhabditis elegans/fisiologia , Moléculas de Adesão Celular Neuronais/metabolismo , Grafite/toxicidade , Interneurônios/fisiologia , Locomoção/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/fisiologia , Interneurônios/efeitos dos fármacos , Mutação/genética , Óxidos/toxicidade
20.
Int Immunopharmacol ; 60: 64-75, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29705531

RESUMO

Arsenic and copper, two ubiquitous pollutants, can be oxidative stress inducers when organisms are heavy or chronically exposed, causing adverse effects on digestion and absorption function, resulting in potential losses to poultry husbandry. The present study examined the effects of arsenic trioxide (30 mg/kg)- and copper sulfate (300 mg/kg)-mixed foods, administered alone or in combination for 12 weeks, on various biochemical indices of oxidative stress and immunity in the small intestines of Hy-line chickens. The results showed that for the first four weeks of exposure, both the redox and immune systems were unaffected. Subsequently, exposure to arsenic or copper significantly increased the level of lipid peroxidation (malondialdehyde and ability of anti-hydroxy radical) concomitant with a collapse of the antioxidant system (catalase and glutathione peroxidase), in a time-dependent manner. An increase in the mRNA and protein levels of pro-inflammatory indicators (nuclear factor kappa B, cyclooxygenases-2, tumor necrosis factor-α and prostaglandin E2 synthases) with a definite tendency toward Th1 (Th, helper T cell) cytokines was observed in both arsenic and copper treated chickens. Histologically, the destruction of the biofilm structure and inflammatory infiltrates was observed. Thus, in the intestine, heat shock proteins play protective roles against tissue damage. In some cases, we observed that the tissues of the small intestine were more sensitive to arsenic than to copper. Moreover, co-exposure induced more serious intestinal toxicity than single treatment group, and this mechanism needs further exploration.


Assuntos
Sulfato de Cobre/toxicidade , Intestinos/efeitos dos fármacos , Óxidos/toxicidade , Animais , Trióxido de Arsênio , Arsenicais , Galinhas , Citocinas/genética , Citocinas/metabolismo , Proteínas de Choque Térmico/genética , Mucosa Intestinal/metabolismo , Intestinos/patologia , Intestinos/ultraestrutura , Masculino , Estresse Oxidativo/efeitos dos fármacos
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